Composition for preventing or treating keloids or hypertrophic scars

ABSTRACT

The present invention relates to a pharmaceutical composition for preventing or treating hypertrophic scars. The present inventors have found that the inhibition of expression of TXNDC5, PRRC1, S100A11, Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 can be a new target for improving and treating hypertrophic scars. In the present invention, TXNDC5-, PRRC1-, S100A11-, Galectin 1-, Filamin A-, eIF-5A-, Annexin A2-, and FABP5-specific siRNAs were constructed to determine the probability of treating the hypertrophic scars. As a result, the knockdown of the protein or a gene encoding the protein induces apoptosis in the hypertrophic scars and reduces collagen expression, which can be very useful in treating wounds.

TECHNICAL FIELD

The present invention relates to a composition for preventing ortreating keloids or hypertrophic scars.

BACKGROUND ART

When a dermal layer located deep in the skin is damaged due to surgeryor trauma, collagen needed to maintain tension of the skin proliferatesexcessively in the dermal layer so that the collagen emerges from thethin skin even after a wound has healed, leaving a wound-healed scar inthe skin, which is referred to “normal scar.” This appears as a resultof wound healing, but hypertrophic scars or keloids may appear becausefibrous tissues grow abnormally in a compact manner when the skin has adysfunction in properly regulating and inhibiting a wound healingprocess. The hypertrophic scars are different from the keloids in thatthe hypertrophic scars do not extend beyond a wound area and tend togradually disappear over time, but the keloids grow wider than a damagedarea and penetrate into a normal skin over time. There have been variousattempts to treat the hypertrophic scars or keloids, including surgicaltherapy, radiotherapy, steroid therapy, occlusive dressing with siliconegel, laser therapy, and the like, but these methods have limitedeffects. Accordingly, there are no established methods.

It was known that hypertrophic scars or keloids are formed due to theexcessive accumulation of collagen when movement of cells isoveractivated during a wound healing process, or when the collagen isformed excessively or is not degraded normally as the cells andcapillary vessels proliferate abnormally. Registered Korean Patent No.10-1505294 discloses a starfish-enriched liquid extract that may be usedto hydrolyze collagen to reduce the formation of scars, and RegisteredKorean Patent No. 10-1697396 discloses a method of treating ahypertrophic scar using a compound that targets a connective tissuegrowth factor (CTGF) associated with fibrosis.

There is little information on biomarkers that participate in formationof collagen, which excessively accumulates during the wound healingprocess, and proliferation of cells. By selecting such a biomarker toexactly diagnose an abnormal scar such as a hypertrophic scar andscreening a material targeting the biomarker, there is a possibletreatment which inhibits the formation of hypertrophic scars or keloids.

DISCLOSURE Technical Problem

Therefore, it is an object of the present invention to provide apharmaceutical composition for preventing or treating keloids orhypertrophic scars.

It is another aspect of the present invention to provide a method ofpreventing or treating keloids or hypertrophic scars.

It is still another aspect of the present invention to provide a methodof screening a material for preventing or treating keloids orhypertrophic scars.

It is yet another aspect of the present invention to provide a method ofdiagnosing keloids or hypertrophic scars.

Technical Solution

To achieve the above objects, the present inventors have assumed that aprotein marker having an abnormal expression pattern causes ahypertrophic scar by comparing a difference in expression of variousproteins observed in hypertrophic scar tissues and normal tissues, andselected proteins having an expression pattern different from those inthe normal tissues.

Accordingly, one aspect of the present invention provides a compositionfor diagnosing keloids or hypertrophic scars, which includes a materialused to measure an expression level of one or more genes selected fromthe group consisting of TXNDC5, PRRC1, S100A11, Galectin 1, Filamin A,eIF-5A, Annexin A2, and FABP5 or an expression level of one or moreproteins selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5.

Another aspect of the present invention provides a method of diagnosingkeloids or hypertrophic scars, which includes:

measuring an expression level of one or more genes selected from thegroup consisting of TXNDC5, PRRC1, S100A11, Galectin 1, Filamin A,eIF-5A, Annexin A2, and FABP5 or an expression level of one or moreproteins selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 in keloid orhypertrophic scar tissues; and

comparing the results of measurement with the expression levels of thegenes or proteins in normal tissue.

The measurement of the expression levels of the genes or proteins may becarried out using various methods known in the related art. For example,the measurement may be carried out using RT-PCR (Sambrook et. al.,Molecular Cloning. A Laboratory Manual, 3rd ed. Cold Spring Harbor Press(2001)), Northern blotting (Peter B. Kaufman et al., Molecular andCellular Methods in Biology and Medicine, 102-108, CRC press), ahybridization reaction using a cDNA microarray (Sambrook et. al.,Molecular Cloning. A Laboratory Manual, 3rd ed. Cold Spring Harbor Press(2001)), Western blotting, or an in situ hybridization reaction(Sambrook et. al., Molecular Cloning. A Laboratory Manual, 3rd ed. ColdSpring Harbor Press (2001)).

Also, the present inventors have confirmed the expression of theselected proteins in keloid or hypertrophic scar tissues and normaltissues using Western blotting and immunohistochemical staining. It wasconfirmed that when each of genes encoding the proteins is knocked downin the keloid or hypertrophic scar tissues, the expression of collagentype I, α-SMA and PCNA proteins was reduced. These results support thatinhibition of the proteins or the knockdown of the genes encoding theproteins is very useful in treating keloids or hypertrophic scars.

Accordingly, still another aspect of the present invention provides apharmaceutical composition for preventing or treating keloids orhypertrophic scars, which includes, as an active ingredient, a materialthat inhibits the expression of one or more genes selected from thegroup consisting of TXNDC5, PRRC1, S100A11, Galectin 1, Filamin A,eIF-5A, Annexin A2, and FABP5 or inhibits the activity of one or moreproteins selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5.

Yet another aspect of the present invention provides a method oftreating a subject having a keloid disease or hypertrophic scar, whichincludes:

(a) administering a pharmaceutical composition, which comprises, as anactive ingredient, a material that inhibits the expression of one ormore genes selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 or inhibits theactivity of one or more proteins selected from the group consisting ofTXNDC5, PRRC1, S100A11, Galectin 1, Filamin A, eIF-5A, Annexin A2, andFABP5, to the subject having a hypertrophic scar or keloid wound.

In the present invention, the material that inhibits the expression ofone or more genes selected from the group consisting of TXNDC5, PRRC1,S100A11, Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 mayinclude short hairpin RNA (shRNA), small interfering RNA (siRNA),microRNA (miRNA), Crispr/Cas9, Crispr/Cpf1, a ribozyme, a DNAzyme, apeptide nucleic acid (PNA), an antisense oligonucleotide, and thematerial that inhibits the activity of the proteins expressed by thegenes may include an antibody, an aptamer, a natural extract, or achemical. In this case, any material may be included without limitationas long as it is a material that inhibits the expression of the genesand the activity of the proteins.

The term “short hairpin RNA or shRNA” used in this specification refersto single-stranded RNA having a length of 45 to 70 nucleotides. Here, anoligo DNA serving to connect a 3- to 10-base linker between a sensestrand of a siRNA base sequence of a target gene and a nonsense strandcomplementary to the sense strand is synthesized, and then cloned into aplasmid vector, or shRNA is inserted into a retrovirus such as alentivirus and an adenovirus, and expressed to form shRNA having alooped hairpin structure. Then, the shRNA is converted into siRNA by anintracellular dicer to show an RNAi effect.

The term “siRNA” used in the present invention refers to a nucleic acidmolecule that may mediate RNA interference or gene silencing (see WO00/44895, WO 01/36646, WO 99/32619, WO 01/29058, WO 99/07409, and WO00/44914). Because the siRNA may inhibit the expression of a targetgene, the siRNA is provided for an effective gene knockdown method or agene therapy method. Although siRNA was first found in plants, insects,Drosophila, and parasites, a variety of siRNAs have been developed andused for application to mammalian cell research (Degot S, et al. 2002;Degot S, et al. 2004; Ballut L, et al. 2005).

A siRNA molecule of the present invention may have a structure in whicha sense strand (a sequence corresponding to an mRNA sequence of eachgene) and an antisense strand (a sequence complementary to an mRNAsequence of each gene) are located opposite each other to form a doublestranded structure. Alternatively, the siRNA molecule of the presentinvention may have a single chain structure having a self-complementarysense strand and an antisense strand. The siRNA may include, but is notlimited to, a complete pair of a double-stranded RNA region forming RNApairs, as well as unpaired regions formed by a mismatch (thecorresponding bases are not complementary to each other), a bulge (thereare no corresponding bases in a one-way strand), and the like. The fulllength of siRNA is in a range of 10 to 100 bases, preferably 15 to 80bases, more preferably 20 to 70 bases, and most preferably 20 to 30bases.

The term, “microRNA or miRNA” used in this specification refers to asingle-stranded RNA molecule having a length of 21 to 25 nucleotides,and is a regulatory substance that controls the expression of genes ineukaryotes by inhibiting a target mRNA in a disruption or translationphase. Such miRNA is formed by two-step processing. A primary miRNAtranscript is cleaved in the nuclei by an RNase III type enzyme referredto as Drosha, resulting in a stem-loop structure consisting of 70 to 90bases, that is, premiRNA. Then, the premiRNA is translocated into thecytoplasm, and cleaved by an enzyme referred to as a dicer to formmature miRNA consisting of 21 to 25 bases. The miRNA thus formedcomplementarily binds to a target mRNA to serve as apost-transcriptional gene suppressor and induce translational inhibitionand mRNA destabilization. The miRNA is involved in various physiologicalphenomena and the onset of diseases.

The term “antisense oligonucleotide” used in this specification refersto DNA or RNA, or a derivative thereof, which contains a nucleic acidsequence complementary to a certain mRNA sequence, and serves to bind toa complementary sequence in the mRNA in order to inhibit translation ofmRNA into a protein. The antisense sequence of the present inventionrefers to a DNA or RNA sequence that is complementary to each of thegenes, and may bind to mRNA of each of the genes. In this case, theantisense sequence may inhibit essential activities of translation ofmRNA of each of genes, translocation into the cytoplasm, maturation, orother overall biological functions. An antisense nucleic acid sequencemay have a length of 6 to 100 bases, preferably 8 to 60 bases, and morepreferably 10 to 40 bases.

According to one embodiment of the present invention, the material maybe siRNA. More specifically, siRNA used to cause the knockdown ofTXDNC-5 may consist of sense 5′-GGCCCUAACUAGAGUUCUAtt-3′ (SEQ ID NO: 1)and antisense 5′-UAGAACUCUAGUUAGGGCCtt-3′ (SEQ ID NO: 2); two siRNAsused to cause the knockdown of PRRC1 may consist of sense5′-CAAGAAGACCCUAGAAUUAtt-3′ (SEQ ID NO: 3) and antisense5′-UAAUUCUAGGGUCUUCUUGtt-3′ (SEQ ID NO: 4), and sense5′-UAUCAAAUCUGGUGAAtt-3′ (SEQ ID NO: 5) and antisense siRNAUUCACCUCCAGAUUUGAUAtt-3′ (SEQ ID NO: 6); and siRNA used to cause theknockdown of S100A11 may consist of sense GAACUAGCUGCCACAAtt-3′(SEQ IDNO: 7) and antisense 5′-UUGUGAAGGCAGCUAGUUCtt-3′(SEQ ID NO: 8).

In this specification, the term “treatment” refers to (i) prevention ofkeloids or hypertrophic scars; (ii) inhibition of formation orimprovement of keloids or hypertrophic scars; and (iii) alleviation ofdisorders or diseases associated with the inhibition of formation orimprovement of keloids or hypertrophic scars. Therefore, in thisspecification, the term “therapeutically effective amount” refers to anamount sufficient to achieve the pharmacological effect.

According to another aspect of the present invention, the presentinvention provides a pharmaceutical composition for preventing ortreating keloid diseases or hypertrophic scars, which includes (a) atherapeutically effective amount of, as an active ingredient, a materialthat inhibits the expression of one or more genes selected from thegroup consisting of TXNDC5, PRRC1, S100A11, Galectin 1, Filamin A,eIF-5A, Annexin A2, and FABP5 or inhibits the activity of one or moreproteins selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5; and (b) apharmaceutically acceptable carrier.

The pharmaceutically acceptable carrier included in the composition ofthe present invention is typically used in preparations, and includeslactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum,calcium phosphate, alginates, gelatin, calcium silicate,microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water,syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate,talc, magnesium stearate, and mineral oil, but the present invention isnot limited thereto. In addition to the aforementioned components, thepharmaceutical composition of the present invention may further includea lubricant, a wetting agent, a sweetening agent, a flavoring agent, anemulsifying agent, a suspending agent, a preservative, and the like.

The pharmaceutical composition of the present invention is preferablyparenterally administered. For example, the pharmaceutical compositionmay be administered by intravenous, intraperitoneal, intratumoral,intramuscular, subcutaneous, hepatoportal, hepatoarterial, or localadministration.

An appropriate dose of the pharmaceutical composition of the presentinvention may vary depending on factors such as a preparation method, amode of administration, the age, weight, and sex of a patient, theseverity of symptoms of a disease, a diet, duration of administration, aroute of administration, a secretion rate, and responsiveness.Generally, a skilled physician may easily determine and prescribe thedose of the composition effective for desired treatment.

The pharmaceutical composition of the present invention may beformulated using a pharmaceutically acceptable carrier and/or excipient,according to methods which may be easily carried out by a person havingordinary skill in the art to which the present invention belongs, sothat the pharmaceutical composition is prepared in a unit dosage form,or may be prepared by incorporation into a high-dose container. In thiscase, a formulation may be in the form of a solution, a suspension or anemulsion in an oily or aqueous medium, or in the form of an extract, apowder, a granule, a tablet or a capsule, and may further include adispersing agent or a stabilizing agent.

The pharmaceutical composition of the present invention may be used as askin preparation for external use for alleviating or treating keloids orhypertrophic scars. In this case, the formulation is used withoutparticular limitation depending on the body part. Specifically, thepharmaceutical composition may be, for example, a cosmetic compositionhaving a formulation such as a skin softener, a nutrition toner, amassage cream, a nutrition cream, a pack, a gel, or a skin-adhesive typecosmetic product. Also, the pharmaceutical composition may be aformulation for percutaneous administration such as a lotion, anointment, a gel, a cream, a patch, or a spray. For the composition forexternal use with each formulation, a person having ordinary skill inthe art may properly select and blend the other components other thanthe aforementioned components in the pharmaceutical composition of thepresent invention without any difficulty, depending on other factorssuch as an external formulation for skin, a purpose of use, or the like.In this case, the pharmaceutical composition may have a synergisticeffect when the components are used together with the other basematerials.

Also, the present invention provides a method of screening a materialfor preventing or treating keloid diseases or hypertrophic scars, whichincludes the following steps:

(a) treating keloid tissues or keloid cells with a test material; and

(b) analyzing the activity of one or more intracellular proteinsselected from the group consisting of TXNDC5, PRRC1, S100A11, Galectin1, Filamin A, eIF-5A, Annexin A2, and FABP5 in the tissues or cellstreated with the test material or analyzing an expression level of genesencoding the proteins, wherein the test material is judged to be amaterial for preventing or treating keloids or hypertrophic scars whenthe activity of the proteins or the expression pattern of the genesencoding the proteins in normal tissues is different from that in thetissues or cells treated with the test material.

According to the method of the present invention, first of all, a testmaterial to be tested is brought into contact with keloid orhypertrophic scar tissues. In describing a screening method of thepresent invention, the term “test material” used herein refers to anunknown material that is used for screening in order to check whether ithas an influence on an expression level of the genes or an amount oractivity of the proteins. The test material includes chemicals,nucleotides, antisense RNA, shRNA, miRNA, small interfering RNA (siRNA),and natural extracts, but the present invention is not limited thereto.

Next, the intracellular expression levels of the genes and proteinsthereof are analyzed in the tissues or cells treated with the testmaterial. As a result of measurement, when the intracellular expressionof genes is reduced, or the activity or expression of the proteins isreduced, the test material may be judged to be a material for preventingor treating keloids or hypertrophic scars.

Advantageous Effects

According to the present invention, by identifying a protein which isinvolved in abnormal collagen formation in a wound area that may causekeloid or hypertrophic scars, the hypertrophic scars can be accuratelydiagnosed using the corresponding protein and a gene encoding theprotein. Also, a material that inhibits the expression and activity ofthe proteins or genes can be provided, and thus effectively used toalleviate and treat the keloid or hypertrophic scars.

DESCRIPTION OF DRAWINGS

FIG. 1 shows the results of immunohistochemical staining for candidateproteins of human hypertrophic scar tissue.

FIG. 2 shows the results of determining protein knockdown efficiencywhen siRNA targeting three candidate proteins is treated, using Westernblotting.

FIG. 3 shows the results of determining an expression pattern ofcollagen in hypertrophic scar tissues in which the candidate protein isknocked down, using Western blotting.

BEST MODE

Hereinafter, the present invention will be described in further detailwith reference to embodiments thereof. However, it will be apparent tothose skilled in the art that that the description proposed herein isjust a preferable example for the purpose of illustration only and isnot intended to limit the scope of the present invention.

EXAMPLES

Preparation of Human Skin Fibroblasts, Normal Tissues, and HypertrophicScar Tissues

Skin tissues used in this experiment were obtained from a total of threepatients, and an immunohistochemical (IHC) experiment was conductedusing male and female normal tissues and scar tissues. Then, an effectof siRNA transformation was observed using primary fibroblast cellsderived from each of the tissues.

A tissue was washed with 70% ethanol, and fats were removed by trimming.Then, the tissue was chopped to separate a tissue for the MC experiment.The remaining tissue was further trimmed, and then chopped. A mixedsolution including collagenase, trypsin, and EDTA was added to thetissue, and the cells were isolated by centrifugation at 37° C. and 100rpm. The isolated cells were cultured in an F12 medium supplanted with10% fetal bovine serum (FBS) and gentamycin.

Comparison of Expression of Candidate Proteins Via Immunohistochemical(IHC) Experiment on Hypertrophic Scar Tissues

A tissue obtained by biopsy was added to an O.C.T compound (Cell Poth,KMA-0100-OOA), and frozen in dry ice. The frozen tissue was fixed in abuffer containing acetone and methanol at a ratio of 1:1. After thebuffer was removed, the tissue was permeabilized by treatment with 0.5%Triton X-100 at room temperature for 10 minutes, and peroxidase activitywas then inhibited using Ultravision hydrogen peroxide (Thermokit/Ultravision LP detection system). The tissue was reacted with anUltravision block buffer at room temperature for 10 minutes, and thentreated with the corresponding primary antibody, and treated overnightat 4° C. Each of TXNDC5 (Abcam, Ab155684), PRRC1 (Abcam/ab12544),S100A11 (Abcam/ab97329), Galectin 1 (Abcam, Ab108389), Filamin A(Millipore/MAB1680), eIF5-A (Abcam/ab32014), Annexin A2 (CellSignaling/8235), and FABP5 (Abcam/ab37267) was used as the primaryantibody. The tissue was treated with a primary antibody enhancer atroom temperature for 10 minutes, and a HRP polymer was reacted at roomtemperature for 15 minutes in the dark. After the HRP polymer wasremoved, all the tissues except for PRRC1 were treated with AEC (Spring,ASS-125), and PRRC1 was treated with DAB (Thermo, TA-125-HDX) for aminute. The tissues were stained with Mayer's hematoxylin at roomtemperature, dehydrated, and then mounted with Canada balsam-mixedxylene. Then, the tissues were observed using a microscope.

The IHC results showed that TXNDC5, PRRC1, S100A11, Galectin 1, FilaminA, eIF-5A, Annexin A2, and FABP5 had a pattern of increased expressionin the hypertrophic scar tissues, compared to the normal tissues. Thepattern of increased expression varied depending on the locations of thedermis, the epidermis, and other layers. The results of difference inexpression of the candidate proteins are listed in Table 1 and shown inFIG. 1 below.

TABLE 1 Results of comparison of expression and location of humanfibroblast normal/scar pair proteins Candidate Results of difference inexpression TXNDC5 Increased expression in scar epidermis and dermisPRRC1 Increased expression in scar epidermis and dermis S100A11Increased expression in scar epidermis and dermis Galectin 1 Increasedexpression in scar dermis Filamin A Increased expression in scarepidermis and dermis eIF-5A Increased expression in scar epidermis anddermis Annexin A2 Increased expression in scar epidermis and dermisFABP5 Increased expression in scar epidermis

Change in Effect of Candidate Protein-Specific siRNATransformation—Changes in Expression of Collagen Type I and a-SMA andPCNA in Fibroblasts of Hypertrophic Scar Tissues

For three (TXNDC5, PRRC1, and S100A11) of the proteins selected from theIHC results, expression of proteins associated with proliferation ofcollagen and fibroblasts, which were excessively expressed in a scarwhen the expression of each of the genes was knocked down using siRNA,was analyzed.

Specifically, sense 5′-GGCCCUAACUAGAGUUCUAtt-3′ (SEQ ID NO: 1) andantisense 5′-UAGAACUCUAGUUAGGGCCtt-3′ (SEQ ID NO: 2) were used as siRNAused to cause the knockdown of TXDNC-5; sense5′-CAAGAAGACCCUAGAAUUAtt-3′ (SEQ ID NO: 3) and antisense5′-UAAUUCUAGGGUCUUCUUGtt-3′ (SEQ ID NO: 4), and sense5′-UAUCAAAUCUGGUGAAtt-3′ (SEQ ID NO: 5) and antisense siRNAUUCACCUCCAGAUUUGAUAtt-3′ (SEQ ID NO: 6) were used as two siRNAs used tocause the knockdown of PRRC1; and sense GAACUAGCUGCCACAAtt-3′ (SEQ IDNO: 7) and antisense 5′-UUGUGAAGGCAGCUAGUUCtt-3′ (SEQ ID NO: 8) wereused as siRNA used to cause the knockdown of S100A11.

Specifically, fibroblasts isolated from hypertrophic scar tissues werecultured in an F12 medium supplemented with 10% FBS, and thentransfected with the siRNA knocking down the corresponding protein.After 48 hours of siRNA transfection, a cell lysate was extracted, andthen subjected to Western blotting to check a change in expression ofcollagen, and the like.

As a result, it was confirmed that the target protein was knocked downby the siRNA transfection (FIG. 2), and an effect of the knockdown ofthe target protein on the functions and growth of fibroblasts waschecked with a change in expression of the collagen-1, α-SMA, and PCNAproteins.

Based on the results of observation, it was confirmed that theexpression of the collagen-1, α-SMA, and PCNA proteins was inhibitedwhen the expression of all the three genes was inhibited (FIG. 3).

As a result, it was confirmed that, by inhibiting each of the candidateproteins, since the synthesis of collagen excessively formed in thehypertrophic scars was inhibited, the growth of fibroblasts waseffectively inhibited and apoptosis was induced, the candidate proteinswere found to be targets for alleviating or treating the hypertrophicscars.

While the present invention has been shown and described with referenceto certain exemplary embodiments thereof, it will be understood by thoseskilled in the art that various changes in form and details may be madetherein without departing from the scope of the invention as defined bythe appended claims. Therefore, it will be understood that the practicalscope of the present invention is defined by the appended claims andequivalents thereof.

What is claimed is:
 1. A pharmaceutical composition for preventing ortreating keloids or hypertrophic scars comprising, as an activeingredient, a material that inhibits the activity of one or moreproteins selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 or inhibits theexpression of genes encoding the one or more proteins.
 2. Thepharmaceutical composition of claim 1, wherein the active ingredientcomprises shRNA, siRNA, miRNA, an antisense oligonucleotide, a ribozyme,Crispr/Cas9, a DNAzyme, a peptide nucleic acid (PNA), a peptide, anantibody, an aptamer, a natural extract, or a chemical.
 3. Thepharmaceutical composition of claim 2, wherein the active ingredientcomprises shRNA, siRNA, miRNA, or an antisense oligonucleotide, whichinhibits the expression of the genes.
 4. A method of screening amaterial for preventing or treating keloids or hypertrophic scar,comprising: (a) treating tissues derived from a patient with keloids orhypertrophic scars with a test material; and (b) analyzing the activityof one or more proteins selected from the group consisting of TXNDC5,PRRC1, S100A11, Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 oranalyzing an expression level of genes encoding the proteins in thetissues or cells treated with the test material, wherein the testmaterial is judged to be a material for preventing or treating keloidsor hypertrophic scars when the activity of the proteins or theexpression pattern of the genes encoding the proteins in the tissues orcells treated with the test material is different from that in normaltissues.
 5. A composition for diagnosing keloids or hypertrophic scars,comprising a material used to measure an expression level of one or moregenes selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5, or an expressionlevel of one or more proteins selected from the group consisting ofTXNDC5, PRRC1, S100A11, Galectin 1, Filamin A, eIF-5A, Annexin A2, andFABP5.
 6. A method of diagnosing keloids or hypertrophic scars,comprising: measuring an expression level of one or more genes selectedfrom the group consisting of TXNDC5, PRRC1, S100A11, Galectin 1, FilaminA, eIF-5A, Annexin A2, and FABP5 or an expression level of one or moreproteins selected from the group consisting of TXNDC5, PRRC1, S100A11,Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 in a sampleobtained from a subject having or expecting to have a keloid orhypertrophic scar; and comparing the results of measurement with theexpression levels of the genes or proteins in the sample from the normalsubject.
 7. A method of treating a subject having a keloid orhypertrophic scar, comprising: (a) administering a pharmaceuticalcomposition, which comprises, as an active ingredient, a material thatinhibits the expression of one or more genes selected from the groupconsisting of TXNDC5, PRRC1, S100A11, Galectin 1, Filamin A, eIF-5A,Annexin A2, and FABP5 or inhibits the activity of one or more proteinsselected from the group consisting of TXNDC5, PRRC1, S100A11, Galectin1, Filamin A, eIF-5A, Annexin A2, and FABP5, to the subject having akeloid or hypertrophic scar.